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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/28230015/screening-of-gene-mutations-associated-with-bone-metastasis-in-nonsmall-cell-lung-cancer
#1
Kun Zhang, Min Zhang, Jinlong Zhu, Wang Hong
OBJECTIVE: The objective of this study is to assess the gene mutation of advanced nonsmall cell lung cancer (NSCLC) patients with bone metastasis using next-generation sequencing (NGS), and screen for the driver genes which are associated with bone metastasis of lung cancer. MATERIALS AND METHODS: Eight clinicopathologic samples from advanced NSCLC combined with bone metastasis patients were collected. Exome sequencing was conducted within 483 tumor-associated genes using Hiseq 2000_PE75 NGS platform...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28223509/high-throughput-screening-of-rare-metabolically-active-tumor-cells-in-pleural-effusion-and-peripheral-blood-of-lung-cancer-patients
#2
Yin Tang, Zhuo Wang, Ziming Li, Jungwoo Kim, Yuliang Deng, Yan Li, James R Heath, Wei Wei, Shun Lu, Qihui Shi
Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219200/-application-strategies-of-the-third-generation-egfr-tki-in-the-context-of-precision-medicine
#3
J Zhao, S J Zhang, C C Zhou
With the advances in molecular detection technology and the emergence of various targeted agents, we have entered the era of precision medicine across the whole process of cancer diagnosis and treatment. Tyrosine kinase inhibitors targeting epidermal growth factor receptor gene mutation, the most common driver, have been developed from the first generation to the third generation, improving the survival and life quality of patients with advanced non-small cell lung cancer. It is critically important how to rank these targeted agents and arrange combination therapies, and this review will focus on the strategies of the third-generation EGFR-TKI in the context of precision medicine...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28217439/egfr-targeted-therapy-in-lung-cancer-an-evolving-story
#4
C Bartholomew, L Eastlake, P Dunn, D Yiannakis
Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#5
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28185792/randomized-phase-iii-study-of-docetaxel-plus-cisplatin-versus-pemetrexed-plus-cisplatin-as-first-line-treatment-of-nonsquamous-non-small-cell-lung-cancer-a-trail-trial
#6
Cheol-Kyu Park, In-Jae Oh, Kyu-Sik Kim, Yoo-Duk Choi, Tae-Won Jang, Youn-Seup Kim, Kwan-Ho Lee, Kyeong-Cheol Shin, Chi Young Jung, Sei-Hoon Yang, Jeong-Seon Ryu, Seung-Hun Jang, Seung-Soo Yoo, Suk-Joong Yong, Kye Young Lee, Kwang-Ho In, Min-Ki Lee, Young-Chul Kim
INTRODUCTION: To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer. MATERIALS AND METHODS: A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m(2) with either docetaxel 60 mg/m(2) (n = 71) or pemetrexed 500 mg/m(2) (n = 77) for ≤ 4 cycles...
January 11, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28179026/proportion-and-clinical-features-of-never-smokers-with-non-small-cell-lung-cancer
#7
Jaeyoung Cho, Sun Mi Choi, Jinwoo Lee, Chang-Hoon Lee, Sang-Min Lee, Dong-Wan Kim, Jae-Joon Yim, Young Tae Kim, Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, Young Sik Park
BACKGROUND: The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution. METHODS: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. RESULTS: Of the 1860 NSCLC patients, 707 (38...
February 8, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28176910/apatinib-as-post-second-line-therapy-in-egfr-wild-type-and-alk-negative-advanced-lung-adenocarcinoma
#8
Shen-Cun Fang, Hai-Tao Zhang, Ying-Ming Zhang, Wei-Ping Xie
In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People's Republic of China for use as a subsequent line of treatment for advanced gastric cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28174389/-molecular-biology-for-surgical-treatment-of-lung-cancer
#9
Kenichi Suda, Tetsuya Mitsudomi
Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28167502/a-genetic-interaction-analysis-identifies-cancer-drivers-that-modify-egfr-dependency
#10
Sida Liao, Teresa Davoli, Yumei Leng, Mamie Z Li, Qikai Xu, Stephen J Elledge
A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which they can substitute for each other have not been systematically explored. To comprehensively investigate how cancer drivers genetically interact, we searched for modifiers of epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, and expression screens in a non-small cell lung cancer (NSCLC) model. We elucidated a broad spectrum of tumor suppressor genes (TSGs) and oncogenes (OGs) that can genetically modify proliferation and survival of cancer cells when EGFR signaling is altered...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167203/erbb2-mutated-metastatic-non-small-cell-lung-cancer-response-and-resistance-to-targeted-therapies
#11
Jody C Chuang, Henning Stehr, Ying Liang, Millie Das, Jane Huang, Maximilian Diehn, Heather A Wakelee, Joel W Neal
ERBB2/HER2 has long been recognized as an oncogenic driver in some breast and gastro-esophageal cancers, in which amplification of this gene confers sensitivity to treatment with ERBB2 directed agents. More recently, somatic mutations in ERBB2 have been reported in 1-2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies. Here we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2 targeted therapies...
February 3, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28164087/met-exon-14-juxtamembrane-splicing-mutations-clinical-and-therapeutical-perspectives-for-cancer-therapy
#12
REVIEW
Sara Pilotto, Anastasios Gkountakos, Luisa Carbognin, Aldo Scarpa, Giampaolo Tortora, Emilio Bria
The MET proto-oncogene plays crucial roles in cell growth and proliferation, survival and apoptosis, epithelial-mesenchymal transition (EMT) and invasion, potentially conditioning the development and progression of the carcinogenesis process. The MET-associated aberrant signaling could be triggered by a variety of mechanisms, such as mutations, gene amplification, increased gene copy number and Met/HGF protein expression. Among the various MET alterations, MET exon 14 splicing abnormalities, causing the loss of the Met juxtamembrane (JM) domain, recently emerged as a new potential oncogenic driver and have been identified and validated across different cancer and histology subtypes...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28152008/highly-sensitive-detection-of-a-her2-12-base-pair-duplicated-insertion-mutation-in-lung-cancer-using-the-eprobe-pcr-method
#13
Yoshiaki Takase, Kengo Usui, Kimihiro Shimizu, Yasumasa Kimura, Tatsuo Ichihara, Takahiro Ohkawa, Jun Atsumi, Yasuaki Enokida, Seshiru Nakazawa, Kai Obayashi, Yoichi Ohtaki, Toshiteru Nagashima, Yasumasa Mitani, Izumi Takeyoshi
Somatic mutation in human epidermal growth factor receptor-related 2 gene (HER2) is one of the driver mutations in lung cancer. HER2 mutations are found in about 2% of lung adenocarcinomas (ADCs). Previous reports have been based mainly on diagnostic screening by Sanger sequencing or next-generation sequencing (NGS); however, these methods are time-consuming and complicated. We developed a rapid, simple, sensitive mutation detection assay for detecting HER2 12 base pair-duplicated insertion mutation based on the Eprobe-mediated PCR method (Eprobe-PCR) and validated the sensitivity of this assay system for clinical diagnostics...
2017: PloS One
https://www.readbyqxmd.com/read/28146588/the-frequency-and-clinical-impact-of-her2-alterations-in-lung-adenocarcinoma
#14
Eun Kyung Kim, Kyung A Kim, Chang Young Lee, Hyo Sup Shim
Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28135039/clinicopathologic-characteristics-and-outcomes-of-chinese-patients-with-non-small-cell-lung-cancer-and-braf-mutation
#15
Xi Ding, Zengli Zhang, Tao Jiang, Xuefei Li, Chao Zhao, Bo Su, Caicun Zhou
BRAF mutation is one of the important driver oncogene in non-small-cell lung cancer (NSCLC). Data on Chinese patients with BRAF-mutant NSCLC are inadequate. Hence, we conducted this study to investigate the clinicopathologic features and outcomes of Chinese patients with NSCLC and BRAF mutations. We identified patients with BRAF-mutant NSCLC between January 2012 and April 2016. Patient characteristics and treatment outcomes were analyzed. In total, 1680 patients were included. Twenty-eight (1.7%) patients harbored BRAF mutations...
January 30, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28129709/profile-of-the-roche-cobas%C3%A2-egfr-mutation-test-v2-for-non-small-cell-lung-cancer
#16
Umberto Malapelle, Rafael Sirera, Eloísa Jantus-Lewintre, Pablo Reclusa, Silvia Calabuig-Fariñas, Ana Blasco, Pasquale Pisapia, Christian Rolfo, Carlos Camps
The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required...
March 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28129007/a-new-frontier-for-targeted-therapy-in-nsclc-clinical-efficacy-of-pembrolizumab-in-the-inhibition-of-programmed-cell-death-1-pd-1
#17
Raffaele Addeo
Non-small-cell lung cancer (NSCLC) is the main pathological type among lung cancers, and it is often diagnosed at an advanced stage of the disease when it is no longer amenable to curative treatments. During recent decades, the survival rate for lung cancer patients has improved significantly in only those whose tumours harbour a driver mutation. Immune checkpoint inhibition is a promising therapeutic strategy for lung cancer. The Keynote 024 is randomized, open-label, international, phase III study to evaluate the efficacy of pembrolizumab, an antibody directed to programmed death 1 (PD-1), an immune checkpoint inhibitor, compared with platinum-based chemotherapy in patients with previously untreated advanced NSCLC and PD-L1 expression in at least 50% of the tumour cells...
March 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28111120/real-world-eq5d-health-utility-scores-for-patients-with-metastatic-lung-cancer-by-molecular-alteration-and-response-to-therapy
#18
Catherine Labbé, Yvonne Leung, João Gabriel Silva Lemes, Erin Stewart, Catherine Brown, Andrea Perez Cosio, Mark Doherty, Grainne M O'Kane, Devalben Patel, Nicholas Cheng, Mindy Liang, Gursharan Gill, Alexandra Rett, Hiten Naik, Lawson Eng, Nicole Mittmann, Natasha B Leighl, Penelope A Bradbury, Frances A Shepherd, Wei Xu, Geoffrey Liu, Doris Howell
INTRODUCTION: Economic analyses of upcoming treatments for lung cancer benefit from real-world health utility scores (HUSs) in an era of targeted therapy. METHODS: A longitudinal cohort study at Princess Margaret Cancer Centre evaluated 1571 EQ5D-3L-derived HUSs in 475 outpatients with metastatic lung cancer across various disease states. Patients with epidermal growth factor receptor (EGFR) (n = 183) and anaplastic lymphoma kinase (ALK) (n = 38) driver alterations were enriched through targeted enrolment; patients with wild-type non-small-cell lung cancer (WT NSCLC) (n = 224) and small-cell lung cancer (SCLC) (n = 30) were sampled randomly...
December 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28109399/targeting-kras-mutated-non-small-cell-lung-cancer-a-history-of-failures-and-a-future-of-hope-for-a-diverse-entity
#19
REVIEW
Alexios Matikas, Dimitrios Mistriotis, Vasilios Georgoulias, Athanasios Kotsakis
Lung cancer remains the leading cause of cancer-related deaths in both men and women. However, the discovery of several oncogenic driver mutations and the development of immune checkpoint inhibitors resulted in improved clinical outcomes for most patients. Although activating KRAS mutations are the most common recurring molecular events in lung adenocarcinoma, little progress has been made during the past decades with no new agents being approved for this indication. The elucidation of the underlying biology of this diverse patient subgroup offers great potential and renewed hope regarding the rational development, rigorous evaluation and subsequent approval of novel targeted agents and combinations which will effectively suppress compensatory escape routes and the emergence of resistance, issues that have plagued previous attempts...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#20
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1(st)-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics...
January 16, 2017: Journal of Thoracic Oncology
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